ANNEXIN-I DEGRADATION IN BRONCHOALVEOLAR LAVAGE FLUIDS FROM HEALTHY SMOKERS - A POSSIBLE MECHANISM OF INFLAMMATION

Annexin I is a glucocorticoid-inducible, phospholipase A(2)-inhibitory protein and is proposed to have an antiinflammatory role. Although an nexin I is a cytosolic protein, it is found extracellularly in secrete d fluids such as semen. We have examined the expression of annexin I i n bronchoalveolar lavage fluids (BALF) from smokers and nonsmokers to investigate the role of annexin I in the airway. We find that annexin I is secreted in BALF, This secretion is not due to cell death or dama ge, because a cytosolic protein, 3-phosphoglycerate kinase, is not see n in BALF, We observed that BALF from smokers (n = 10) had high protei n concentrations as compared with BALF from nonsmokers (n = 11), Annex in I levels were higher in BALF from smokers compared with nonsmokers. However, in smokers, annexin I was exclusively found in the M-r 34,00 0 form that lacks the M-r 3,000 N-terminal anti-inflammatory peptide. In nonsmokers, both the M-r 37,000 native annexin I and the M-r 34,000 proteolytically cleaved form are present, with the M-r 37,000 form be ing most abundant. The NH2-terminal M-r 3,000 peptide of annexin I exh ibits anti-inflammatory actions (G. Cirino et al. Br. J. Pharmacol., 1 08: 573-574, 1993). Previous studies have implicated neutrophil elasta se as the protease cleaving annexin I to the M-r 34,000 protein. We ob served increased elastase levels in BALF from smokers. However, we fin d no correlation between bronchial sample percent of neutrophils in BA LF and the relative amount of the M-r 34,000 band generated. Our data clearly demonstrate that annexin I is degraded in BALF from smokers, a nd we propose that proteolytic cleavage of annexin I in BALF from smok ers may be a mechanism by which polymorphonuclear neutrophils infiltra te sites of inflammation; thus, inactivation of annexin I in smokers' lungs may lead to chronic and uncontrolled inflammation.